Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes: Pharmacokinetic Studies in Adult Rats
- 113 Downloads
To propose a new and effective dose regimen for stable potassium iodide (KI) repeated prophylaxis in case of prolonged exposure to radioactive iodine.
The pharmacokinetics of iodine was determined in rats by compartmental analyses after intravenous and oral administrations of the optimal dose of 1 mg/kg KI, which was previously selected in a dose-effect study. The thyroid protection against iodine-125 incorporation was followed during 24 h after a single oral dosing of KI. A repeated KI prophylaxis was modeled using initial estimates of iodine pharmacokinetic parameters.
A dose regimen consisting in administrations of 1 mg/kg daily for 8 days was selected and studied. Plasma iodine concentrations predicted by simulation were verified by experimental data and varied after the third dose of KI between 174 and 1190 μg/l. The inhibition study of iodine-125 binding in the thyroid as a function of the time showed that the protection effect of KI could be correlated to stable iodine plasma concentrations. Hence, a theoretical decrease in iodine-125 thyroid uptake from 63 to 88% could be achieved in a 24 h-interval between two KI doses.
Given the satisfactory levels of thyroid protection, this dose regimen could be envisaged in order to extent KI indications for repeated prophylaxis.
Key wordsdose regimen potassium iodide prophylaxis pharmacokinetics pharmacokinetic-pharmacodynamic relationship rats
Acknowledgments and Disclosures
The authors are thankful to the Central Army Pharmacy for providing solutions of KI, Dr. Delphine Denais-Lalieve (DVM), Mélanie Berchet, Amandine Sache, Romain Granger and Frédéric Voyer from the animal experiment support group of IRSN for animal care. These studies were supported by the research program in Nuclear Safety and Radiation Protection of the French National Research Agency (ANR) (contract number ANR-11-RSNR-0019). The authors declared no potential conflicts of interest with respect to research, authorship and publication of this article.
- 2.Shakhtarin VV, Tsyb AF, Stepanenko VF, Orlov MY, Kopecky KJ, Davis S. Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident. Int J Epidemiol. 2003;32:584–91.CrossRefGoogle Scholar
- 5.World Health Organization. Iodine thyroid blocking: guidelines for use in planning for and responding to radiological and nuclear emergencies. Geneva; 2017, p. 46.Google Scholar
- 12.Landon G, Bouvier-Capely C, Legrand A, Sontag T, Finance G, Saint-Hilaire M, et al. Validation and comparison of two calibration methods for themeasurement of stable iodine in the urinary matrix by ICP-MS: standard addition vs external calibration. Am J Anal Chem. 2017;8:245–63.CrossRefGoogle Scholar
- 14.Gabrielsson J, Weiner D. Pharmacokinetics and pharmacodynamic data analysis: concepts and applications. Stockholm: Swedish Academy of Pharmaceutical Sciences; 2016.Google Scholar
- 16.Gabrielsson J, Weiner D. Akaike and Schwarz criteria. Pharmacokinetics and pharmacodynamic data analysis: concepts and applications. Stockholm: Swedish Academy of Pharmaceutical Sciences; 2016. p. 389.Google Scholar
- 18.Abrahamyan HG, Hovhannisyan AS. Comparative pharmacokinetics of iodide anion at administration of iodine preparations. New Armenian Medical J. 2011;5:26–32.Google Scholar
- 27.Abraham GE. Serum inorganic iodide levels following ingestion of a tablet form of Lugol solution: evidence for an enterohepatic circulation of iodine. The Original Internist. 2004;11:29–34.Google Scholar
- 34.Clewell RA, Merrill EA, Yu KO, Mahle DA, Sterner TR, Mattie DR, et al. Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: a physiologically-based pharmacokinetic analysis of perchlorate and iodide kinetics in the rat. Toxicol Sci. 2003;73:235–55.CrossRefGoogle Scholar
- 37.Braverman ER, Blum K, Loeffke B, Baker R, Kreuk F, Yang SP, et al. Managing terrorism or accidental nuclear errors, preparing for iodine-131 emergencies: a comprehensive review. Int J Environ Res Public Health. 2014;11:4158–200.Google Scholar